Editing Cerebral cortex (section)

===Cortical patterning===
[[File:Emx2_and_Pax6_Expression.png|thumb|Depicted in blue, Emx2 is highly expressed at the caudomedial pole and dissipates outward. Pax6 expression is represented in purple and is highly expressed at the rostral lateral pole. (Adapted from Sanes, D., Reh, T., & Harris, W. (2012). ''Development of the Nervous System'' (3rd ed.). Burlington: Elsevier Science)]]
The map of functional cortical areas, which include primary motor and visual cortex, originates from a '[[Protomap (neuroscience)|protomap]]',<ref>{{cite journal | vauthors = Rakic P | title = Specification of cerebral cortical areas | journal = Science | volume = 241 | issue = 4862 | pages = 170–176 | date = July 1988 | pmid = 3291116 | doi = 10.1126/science.3291116 | bibcode = 1988Sci...241..170R }}</ref> which is regulated by molecular signals such as [[fibroblast growth factor]] [[FGF8]] early in embryonic development.<ref>{{cite journal | vauthors = Fukuchi-Shimogori T, Grove EA | title = Neocortex patterning by the secreted signaling molecule FGF8 | journal = Science | volume = 294 | issue = 5544 | pages = 1071–1074 | date = November 2001 | pmid = 11567107 | doi = 10.1126/science.1064252 | s2cid = 14807054 | doi-access = free | bibcode = 2001Sci...294.1071F }}</ref><ref>{{cite journal | vauthors = Garel S, Huffman KJ, Rubenstein JL | title = Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants | journal = Development | volume = 130 | issue = 9 | pages = 1903–1914 | date = May 2003 | pmid = 12642494 | doi = 10.1242/dev.00416 | s2cid = 6533589 | doi-access =  }}</ref> These signals regulate the size, shape, and position of cortical areas on the surface of the cortical primordium, in part by regulating gradients of [[transcription factor]] expression, through a process called [[cortical patterning]]. Examples of such transcription factors include the genes [[EMX2]] and [[PAX6]].<ref>{{cite journal | vauthors = Bishop KM, Goudreau G, O'Leary DD | title = Regulation of area identity in the mammalian neocortex by Emx2 and Pax6 | journal = Science | volume = 288 | issue = 5464 | pages = 344–349 | date = April 2000 | pmid = 10764649 | doi = 10.1126/science.288.5464.344 | bibcode = 2000Sci...288..344B }}</ref> Together, both [[transcription factor]]s form an opposing gradient of expression. [[PAX6|Pax6]] is highly expressed at the [[Anatomical terms of location|rostral lateral]] pole, while [[EMX2|Emx2]] is highly expressed in the [[Anatomical terms of location|caudomedial]] pole. The establishment of this gradient is important for proper development. For example, [[mutation]]s in Pax6 can cause expression levels of Emx2 to expand out of its normal expression domain, which would ultimately lead to an expansion of the areas normally derived from the caudal medial cortex, such as the [[visual cortex]]. On the contrary, if mutations in Emx2 occur, it can cause the Pax6-expressing domain to expand and result in the [[Frontal lobe|frontal]] and [[Motor cortex|motor cortical]] regions enlarging. Therefore, researchers believe that similar gradients and [[Cell signaling|signaling centers]] next to the cortex could contribute to the regional expression of these transcription factors.<ref name="Sanes_2012" />
Two very well studied patterning signals for the cortex include [[Fibroblast growth factor|FGF]] and [[retinoic acid]]. If FGFs are [[Protein production|misexpressed]] in different areas of the developing cortex, [[cortical patterning]] is disrupted. Specifically, when [[FGF8|Fgf8]] is increased in the [[Anatomical terms of location|anterior]] pole, Emx2 is [[Downregulation and upregulation|downregulated]] and a [[caudal (anatomical term)|caudal]] shift in the cortical region occurs. This ultimately causes an expansion of the rostral regions. Therefore, Fgf8 and other FGFs play a role in the regulation of expression of Emx2 and Pax6 and represent how the cerebral cortex can become specialized for different functions.<ref name="Sanes_2012" />

Rapid expansion of the cortical surface area is regulated by the amount of self-renewal of [[radial glial cell]]s and is partly regulated by [[Fibroblast growth factor|FGF]] and [[Notch signaling pathway|Notch genes]].<ref>{{cite journal | vauthors = Rash BG, Lim HD, Breunig JJ, Vaccarino FM | title = FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis | journal = The Journal of Neuroscience | volume = 31 | issue = 43 | pages = 15604–15617 | date = October 2011 | pmid = 22031906 | pmc = 3235689 | doi = 10.1523/jneurosci.4439-11.2011 }}</ref> During the period of cortical neurogenesis and layer formation, many higher mammals begin the process of [[gyrification]], which generates the characteristic folds of the cerebral cortex.<ref>{{cite journal | vauthors = Rajagopalan V, Scott J, Habas PA, Kim K, Corbett-Detig J, Rousseau F, Barkovich AJ, Glenn OA, Studholme C | title = Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero | journal = The Journal of Neuroscience | volume = 31 | issue = 8 | pages = 2878–2887 | date = February 2011 | pmid = 21414909 | pmc = 3093305 | doi = 10.1523/jneurosci.5458-10.2011 }}</ref><ref>{{cite journal | vauthors = Lui JH, Hansen DV, Kriegstein AR | title = Development and evolution of the human neocortex | journal = Cell | volume = 146 | issue = 1 | pages = 18–36 | date = July 2011 | pmid = 21729779 | pmc = 3610574 | doi = 10.1016/j.cell.2011.06.030 }}</ref> Gyrification is regulated by a DNA-associated protein [[Trnp1]]<ref>{{cite journal | vauthors = Stahl R, Walcher T, De Juan Romero C, Pilz GA, Cappello S, Irmler M, Sanz-Aquela JM, Beckers J, Blum R, Borrell V, Götz M | title = Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate | journal = Cell | volume = 153 | issue = 3 | pages = 535–549 | date = April 2013 | pmid = 23622239 | doi = 10.1016/j.cell.2013.03.027 | hdl-access = free | doi-access = free | hdl = 10261/338716 }}</ref> and by FGF and [[Sonic hedgehog|SHH]] signaling.<ref>{{cite journal | vauthors = Wang L, Hou S, Han YG | title = Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex | journal = Nature Neuroscience | volume = 19 | issue = 7 | pages = 888–896 | date = July 2016 | pmid = 27214567 | pmc = 4925239 | doi = 10.1038/nn.4307 }}</ref><ref>{{cite journal | vauthors = Rash BG, Tomasi S, Lim HD, Suh CY, Vaccarino FM | title = Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain | journal = The Journal of Neuroscience | volume = 33 | issue = 26 | pages = 10802–10814 | date = June 2013 | pmid = 23804101 | pmc = 3693057 | doi = 10.1523/JNEUROSCI.3621-12.2013 }}</ref>